Small variations in genetic code, previously thought to be inconsequential, can team up to have a big impact

May 2, 2014
by Robert Perkins

(Medical Xpress)—Scientists at USC have definitively demonstrated that large sets of variations in the genetic code that do not individually appear to have much effect can collectively produce significant changes in an organism's physical characteristics.

Studying the budding yeast Saccharomyces cerevisiae, USC's Matthew B. Taylor and Ian M. Ehrenreich found that the effects of these genetic variants can depend on four or more other variants in an individual's genome.

Most genetic analyses of heritable physical characteristics, including genome-wide association studies in human populations, focus on so-called "additive" variants that have effects that occur regardless of the organism's genetic background. Taylor and Ehrenreich, however, found that higher-order interactions of five or more places along the genome can have major impacts, and may help explain the so-called "missing heritability" problem, in which additive genetic variants do not entirely explain many inherited diseases and traits.

"Studies focused only on additive effects often explain just a fraction of the genetic basis of many traits. The question is, what are we missing?" said Ehrenreich, assistant professor of molecular biology at the USC Dornsife College of Letters, Arts and Sciences, and corresponding author of a paper on the study that was published by PLOS Genetics on May 1.

An alternative view of Taylor and Ehrenreich's findings is that genetic variants that have the potential to cause major changes in an organism's phenotype can be completely canceled out if they occur in the "wrong" genomic background.

"It's exciting to provide a characterized example of how genetic background can influence the effects of mutations. We hope that this will open the door for future studies to tease apart how these complex interactions happen," said Taylor, a PhD student in the Molecular and Computational Biology Section at USC.

Their work could impact genetic mapping studies, suggesting that researchers will need to take an approach to understanding the genotype-phenotype relationship that encompasses complex non-additive effects.

Taylor and Ehrenreich plan to take a closer look at the molecular mechanisms that underlie these interactions, in the hopes of providing basic insights into how they occur in biological systems.

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Conserved molecular mechanisms of epigenetically effected cell type differentiation link the nutrient-dependent pheromone-controlled physiology of sexual reproduction at its advent in yeasts to microbial and mammalian reproduction via what is currently understood about ecological variation and ecological adaptations. Therefore, this article attests to the fallacies of ideas about evolution attributed to beneficial mutations and natural selection. For example, we read that BY has a MUTATION that PREVENTS... (not enables)

Ecologically adapted species diversity is obviously nutrient-dependent and pheromone-controlled via sensing and signaling pathways that link the epigenetic landscape to the physical landscape of DNA in the organized genomes of all species.

You have an ideal setting to lend support to your thesis. Take a look at identical twins' fingerprints during the fingerprint development in the womb.A setting where odors and nutrients are indistinguishable and mutations between the twins virtually non existent.

A universal mechanism giving rise to fingerprint variation exists. How do your assertions give rise to the variation of fingerprints of the twins during pregnancy at the point in time where the fingerprints are no longer alterable?

It's not a thesis and you know that. It's a model for the nutrient-dependent pheromone-controlled differentiation of cell types which are manifested in the morphological and behavioral phenotypes of individuals in organisms from microbes to man. The model begins with one-carbon metabolism, which is linked to DNA methylation, amino acid substitutions and sex differences in the cell types of yeasts at the advent of sexual differentiation.

You fail to rate my comments to the latest research and should not anticipate a kind reply. However, if you explain to me how mutations are naturally selected that somehow contribute to differences in fingerprints, we might have a basis for discussion of your thesis, or beliefs in pseudoscientific nonsense.

So jvk... we know that the farther north a species resides, the more seasonal it's reproduction becomes. Newborns have the best chance of survival if they can grow as much as possible before winter sets in.

This trait is shared by most species and so must have evolved a long long time ago. Species which leave tropical climes and move north, quickly begin to exhibit this behavior, so it is possible that it is epigenetic in origin.

Neanderthal mating was most likely seasonal but ours is decidedly not. Perhaps this has something to do with a diet of seasonally-available foods? If we somehow restricted people to eating only foods that are in season rather than for instance oranges in January, perhaps we can reduce this tropical compulsion to mate anytime, anywhere, anyhow. This would result in a MUCH more peaceful and rational world for a number of reasons.

'Eat like a cave man'. Or we could concoct a virus which would merely implant the requisite genes re dan browns Inferno.

If your intent is to link ecological variation and frugivory in other mammals to cell type differentiation via ecological adaptation and radiation in human populations, you lack details that I have already included in articles on my blog and in a figshare prepublication. How on earth do you get 5 star ratings for your meaningless posts that contain no links to supporting documentation?

The twin setting eliminates mutations for fingerprint variation. There are no differences in odors or nutrients - the twins share the same placenta and amniotic fluid - eliminating any contributing odor or nutrient factor to fingerprint variation.

Your model or a model of evolutionary genetics is expected to explain the fingerprint variations of the twins - the twins setting eliminate those models and all expectation for an explanation for those models.

Fingerprint variation is occurring. Odors, nutrients, sex differences, and mutations as possible sources for the variations are eliminated from the setting the twins enjoy.

How on earth do you get 5 star ratings for your meaningless posts that contain no links to supporting documentation?

You seem adept at repeating your formulae but unable to speculate on real-world conditions.

What causes an animals reproduction to become seasonal? According to your model it's what they eat, yes or no? Humans long ago became able to cultivate and to store foods for the winter. They also switched to a meat-dominated diet. Where is the analogue in the non-human world?

During the Pleistocene our brains doubled in size in a very short time. According to your model this was due to a change in diet. Why didn't other animals who were eating the same things experience similar transformation?

What about the speech centers in our brains? Why didn't animals who are eating the same foods as us, develop the ability to speak? Do you think our domesticated wolves became able to bark because they were eating the same foods that enabled us to speak?

@Ghosttoo repetitious ... LOLthe funniest thing about him denying mutations is this: I asked him once

DOES your model make any changes to the nucleotide sequence of the genome of an organism, virus, or extrachromosomal genetic element?This is a yes or no answer

(this is the definition of mutation) to which jvk answered

YES!--Thanks for asking. If it didn't, there could be no increased organismal-level thermoregulation in species from microbes to man via alterations in hydrogen bonds (glucose & glucose dehydrogenase interactions). Obviously, you must first break the bonds before they can be strengthened

IOW - his model CAUSES MUTATIONS which means he is an idiot. see http://phys.org/n...lts.html for more details. he cannot even understand Lenski's mutation experiment!

If you wanted to know the difference between an original DNA segment and the same DNA segment having been damaged and flawlessly repaired what is the way to determined the original from the flawless replacement?

Of course the standard objection is to assert that between an original and a flawless replacement there is no method of measure to tell apart the original part from a flawless replacement part.

If you assert otherwise you must give researchers a sure fire way to measure the difference between original DNA sequences and their flawless sequence replacements through repair.

The gene expressions arising from non damaged original DNA segments and the flawlessly repaired replacement segments of the same sequence will differ.

In order for the twins fingerprints to match, any DNA damage and sequent repair occurring in one twin...

Since lighting never strikes twice at the exact same place (damage of DNA with subsequent "perfect" repair) the gene expressions of identical D

In order for the twins fingerprints to match, any DNA damage and subsequent repair occurring in one twin ...must be the exact same damage and subsequent repair occurring in the other twin as well.

Since lighting (damage) never strikes twice at the exact same place (in twins) (damage of DNA with subsequent "perfect" repair) the gene expressions of identical twins to build identical fingerprints will differ.

No odor. No food. No sequence alteration. Just perfect repair in the long sequence at different places.

scenario. Is there model for that in the context of fingerprint similarity or differences -- or are you just making it up in the context of all the other pseudoscientific nonsense you and others have been taught to believe in? The article is about natural genetic engineering in yeasts and the molecular mechanisms are conserved in species from microbes to man -- a fact known for more than 2 decades.

After a fertilized embryo divides into two cells the two cells already differ. Those two cells share the same conditions and have the same DNA sequence. No cell division occurs without damage.

All cells have a repair process. That is damage control. What you can not control is where damage occurs (at this stage of development). Since the damage and repair locations of both cells differ, so will the gene expressions of each cell. This not a process for cell differentiation. This is where variation occurs under identical conditions for cells.

Once the organism is mature - becomes mufti-cellular - damage control acquires specificity from the cell differentiation. The cells of organs once damaged are repaired. The repair is always at a level where the functions specific to cell differentiation are preserved.

Fertilization requires two different cell types with nutrient-dependent development and pheromone-controlled recognition of sex differences. We detailed this in our 1996 Hormones and Behavior review: From Fertilization to Adult Sexual Behaviorhttp://www.hawaii...ion.html---------------------------------Thanks for telling everyone how you think constraint-breaking mutations somehow enable biophysically constrained cell type differentiation in species from microbes to man, which all experimental evidence shows is nutrient-dependent and pheromone-controlled.

Please provide a citation that supports your pseudoscientific nonsense. Alternatively, admit that you know nothing about this, since you have made that fact perfectly clear.

Bad wording.After fertilization the cell divides into two cells - embryo splitting. Those two cells are now under the same nutrient-dependent development and pheromone-control environment - the uterus.Or if you will - monozygotic twins sharing the same placenta and amniotic sac.The fingerprints will still differ. Is this difference nutrient-dependent and pheromone-controlled?

Pick out a specific point of my pseudoscience nonsense that needs citation.

Genomic-imprinting is also manifest in specific parts of the X-inactivation region's related XIST gene. Here male- and female-specific methyl-group patterns participate in X-inactivation in females and also in the preferential inactivation of the paternal X in human placentae of female concepti (Harrison, 1989; Monk, 1995). This process indicates that tissues of the early conceptus can sense and react differentially to epigenetic sexual dimorphisms on the female conceptus' own two X chromosomes. Furthermore, variations of X-inactivation patterns often account for traits discordance in monozygotic twin females. In other words, they are often found to have nonidentical patterns of X-inactivation, yielding differing expression of noticeable X-linked traits (Machin, 1996).

Wonderful. Here the source for mismatching patterns of X-inactivation is DNA repair.

Pick out a specific point of my pseudoscience nonsense that needs citation.

Where did the genetically differentiated cell type come from that you are using to explain how they resulted in differentiated cell types? In my model they arise from nutrient-dependent pheromone-controlled asexual reproduction in bacteria.

... you either misunderstand Nei, misunderstand the laws of physics, or both.

I've quoted his textbook for idiot minions in past discussions and included the page number:

"...genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world." - 199

The biophysical constraints on one-carbon metabolism, DNA methylation, and alternative splicings of pre-mRNA that differentiate cell types eliminate mutations, which perturb protein folding, from selection for anything but food that might otherwise lead to organism-level complexity.

I've also quoted from the article by Carl Zimmer that places Nei's textbook in its proper perspective of mutation-driven evolution that "just happens"

You didn't answer my question. Are you interpreting that passage as saying that mutations break the laws of physics? Constraints are not impenetrable barriers. Nei is saying that there's selective pressure against changes in necessary genes, but that can be bypassed by gene duplication so mutations in the copies can persist without dire consequences.

Is this what you're trying to tell us? Gene duplication is nutrient-dependent. Mutations persist... Thus, "...complexity emerges as a side effect, even without natural selection... To some extent, it just happens."

Anyone who wants to try to make sense of that regurgitated nonsense should begin by explaining how perturbed protein folding is beneficial, or how mutations enable organismal complexity, or how anything evolves. We can then compare the explanation to what is known about how ecological variation enables ecological adaptations via nutrient-dependent one-carbon metabolism et al. and the pheromone-controlled physiology of reproduction.

"My work in single molecule biophysics led to the first demonstration of single molecule sequencing, and my research in this field has led me to become deeply involved in human genetics, immunology, and the development of new clinical diagnostics." -- Stephen Quake

This appears to be the most recent refutation of mutation-driven evolution via its integration of biophysical constraints. Like all other refutations, it will no doubt be ignored by evolutionary theorists and anonymous fools.

Anyone who would like to continue touting their pseudoscientific nonsense about mutations, natural selection, and evolution must first address the facts that link the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man via the conserved molecular mechanisms I have detailed in a series of published works with and without co-authors, since 1995.

Thanks for asking. They need only ignore the fact that the hemoblobinopathies, or HB variants, are attibutable to amino acid substitution(s) in either globin chain. Currently, 1,181 total hemoglobin variants have been characterized. http://globin.cse.../counter

The biophysical constraints on the variants are nutrient-dependent and the amino acid substitutions manifest in morphological and behavioral phenotypes are controlled by the physiology of reproduction (e.g., pheromone-controlled).

What made you think an entire industry arose in the absence of a model for cell type differentiation? Did you think, perhaps, that they were ignorant enough to use mutation-driven evolution as a basis for their industry?

A Mutation in a Skin-Specific Isoform of SMARCAD1 Causes Autosomal-Dominant Adermatoglyphia

This is the best I can do in support of mutation-driven evolution.

In fact the precursor to SNP (single nucleotide polymorphisms) are inversions of DNA polymorphisms of DNA segmental isoforms in which the DNA sequence is in no way changed.Only the difference is the original sequence being replaced with an identical copy sequence. The expressions arising from the copy sequence will vary from the original sequence expressions. This is the source of fingerprint variation in monozygotic twins sharing the same placenta and amniotic sac.

Instead of this explanation researchers are content with the explanation that the POSITION of the split embryo will give rise to the variation of the twins fingerprints.

In a way I can sense your frustration and to frustrate you further I can not envision evolution without point mutation.

Of course you can't. However, it has become obvious that ecological variation leads to ecological adaptations via nutrient-dependent DNA methylation and the pheromone-controlled physiology of reproduction in species from microbes to man.

That's why you cannot envision evolution without point mutation. At the level of one-carbon metabolism and biophysically constrained adaptations, there is no such thing as mutations that lead to natural selection and evolution. Thus, you're attempting to substitute pseudoscientific nonsense from population genetics for an explanation of biologically based cause and effect. But, as you know, the substitution of pseudoscientific nonsense has no explanatory power.

Memory and learning have a biologically based cause and effect. Once DNA damage is repaired - replace with a copy of a segment of DNA with the same sequence, the expressions from the copy will differ from the expressions read from the original segment damaged and replaced.The difference in the read out of expressions from the replaced and the original yet identical sequence is the source of natural selection, adaptation and evolution neurologically.

If you say odors and nutrients change the memory and learning in the brain or change the expressions of unaltered DNA sequences having been replaced by repair because of damage you are absolutely correct. DNA methylation follows damage and repair. The function of DNA methylation is to label and preserve where the repairs occurred.

This is the evolution of memory and learning in the brain. Without point mutation.I can not explain missing fingerprints without point mutation - permanent alterations in DNA sequences.

Please explain something with or without point mutations, since I have already detailed how nutrient-dependent pheromone-controlled biodiversity arises from ecological variation that results in ecological adaptations with no need to involve mutations or natural selection and no need to use the term evolution in the context of DNA methylation and ecological adaptations.

How much longer do you intend to ignore my published works, like this one:Nutrient-dependent/pheromone-controlled adaptive evolution: a model.http://www.ncbi.n...24693353

since I have already detailed how nutrient-dependent pheromone-controlled biodiversity arises from ecological variation that results in ecological adaptations with no need to involve mutations or natural selection

@jvkthis is not only fallacious, but a blatant deliberate lie

I asked you

DOES your model make any changes to the nucleotide sequence of the genome of an organism, virus, or extrachromosomal genetic element?This is a yes or no answer

Therefore, by definition, your model creates MUTATIONS and supports evolution and this proves you are blatantly and deliberately lying above. You are deliberately misrepresenting scientific fact & this is also well known to you. You've already admitted this, so that means you are deliberate in your post above.DELIBERATE LIE

Captain Stumpy is an Air Force staff sergeant who knows nothing about biological facts or the basis of evolutionary theory.

"[W]hat Haldane, Fisher, Sewell Wright, Hardy, Weinberg et al. did was invent.... The anglophone tradition was taught. I was taught, and so were my contemporaries, and so were the younger scientists. Evolution was defined as "changes in gene frequencies in natural populations." The accumulation of genetic mutations was touted to be enough to change one species to another.... No, it wasn't dishonesty. I think it was wish fulfillment and social momentum. Assumptions, made but not verified, were taught as fact."

Others who became the idiot minions of uninformed biology teachers would long ago have learned that they were taught to believe in pseudoscientific nonsense -- if not for the overwhelming number of idiot minions commenting on topics like this one.

Captain Stumpy is an Air Force staff sergeant who knows nothing about biological facts or the basis of evolutionary theory

I know enough to see when you are lyingI am a paramedic, which is just about as relevant as being a LAB TECHI went to college and graduated with a double major... what about YOU? That's right... you failed out because you could not learn the basics! wasn't that what you said?did you know that in that first year they would have taught you the DEFINITION of MUTATION which is what I used above, straight from NIH and medical dictionaries, of which apparently you have no ability to read or utilize

Tell us jvk, WHY do you ignore the most GLARING and OBVIOUS fact of all, posted above?

AND!SINCE I used the standard definition of mutation as used by geneticists & biologists, and your model creates mutations, which means, by definition, that your model is simply a part of evolution, then WHY are you arguing against YOUR OWN MODEL?

All cells rely on DNA sequence. Neurons are special. You must damage a neurons DNA sequence, and replace (repair) the damaged sequence with the same sequence. The change in expression from exchanging same-DNA-sequenced segments is memory. In a way you inherit the forces an outside environment provides.

Memory that can be created and stored is where expressions of identical DNA sequences change. Those changing expressions are the epigenetic forms of memory, not the underlying DNA sequences. You inherit changed expression with identical sequences of DNA. That's the clue.

The ship of Theseus comes to mind. You can replace every part of the ship (DNA sequences) and the ship remains the ship you started with as long as every part you replace is identical to the part being replaced. The ship's crew (changed expressions) will always change. And different crews on the same ship will navigate the ship differently.

You state that as if you could supply experimental evidence to support your claim. Why don't you try to support it (or learn something about alternative splicings of pre-mRNA)? Instead, you imply that I am wrong about something, but will not address any aspect of my published works.

--------------------------------------Does anyone understand the concept of nutrient-dependent amino acid substitutions, which are responsible for differentiation of cell types in species from microbes to man? Or has everyone been convinced that the pseudoscientific nonsense of mutation-driven biodiversity is an accurate representation?

"Three studies have characterized the full complement of RNA folding in cells. They find large numbers of secondary structures in RNA, some of which may have functional consequences for the cell." http://www.nature...21a.html

You previously reported that you were a "truck captain" who appeared to have been brain damaged by an explosion. I have repeatedly reported that I am a medical laboratory scientist with a history of published works that includes award-winning publications in social science and neuroscience. My claims are readily supported by information that is freely available.

Your nonsensical claims are made anonymously, which means you can claim anything you wish -- except to be capable of intelligent dialogue on this topic or any other that involves current knowledge of epigenetics and genetics.

When one or more of the other three nucleotides are found at a location at more than random frequency, the difference is referred to as a polymorphism rather than a mutation. In my model, single nucleotide polymorphisms lead to nutrient-dependent pheromone-controlled ecological adaptations. Mutations lead to diseases.

your web site says American Medical Technologists (Medical technologist) as well as American Society for Clinical Pathology (Medical laboratory scientist) this second one is misleading to the general public, as you can see at this link http://www.ascp.o...r-centerbasically, you are a glorified lab techespecially as you have no bach degree behind yougiven that it doesn't necesarily take a degree to publish, then that makes you a wana be scientist with a lucky streak hanging on to all the right people

Your nonsensical claims are made anonymously

Nope. anonymous means you cant find me by my moniker, whereas my call sign is not only registered, but also a part of my paperwork and on my certificationsse IFSAC, IAFF, NASA and DOD certsNot non-sense if you can PROVE something. its EMPIRICAL DATA

which means you can claim anything you wish -- except to be capable of intelligent dialogue on this topic or any other that involves current knowledge of epigenetics and genetics

@jkto continuegiven that any semi-capable internet user can find my information with a cursory 10 minute search and verify who I am (Otto did it in less than 3 minutes) then that makes you computer illiterate as wellNow, given that I have some background in the medical field, as well as a 2 degrees and I am posting information that is ALSO readily available, EVEN TO YOU, and you still not only IGNORE IT, but argue against it, it appears that you are the one incapable of intelligent dialoguedispute it. It will only reflect on your poor argument, as I USED YOUR OWN WORDS as proof, as well as YOUR OWN ADMISSIONS as proof

Thanks for playing, sparky. you really should have gotten your education. you could have actually done something important instead of making perfume and arguing pseudoscience

your ASSumption that mutations can only lead to disease is proof positive that you are NOT a scientistGiven that http://phys.org/n...lts.html shows positive proof that mutations can be selected for positive results, your observation above only stands to support my conclusions that you are attempting to push pseudoscience as well as argue against your own model,which, by your own admission, causes MUTATIONS per the definition of the word (which you even agreed with)Therefore you argue, logically, that your own model only creates only disease OR that you are not capable of being objective to scienceOR you are not able to comprehend the lexicon of your own field (which has already been proven elsewhere: see my other link above)

Given that you ignore EMPIRICAL DATA that does not support your conclusions as well as misrepresent data and facts, I figure it is the last two.

Those who do not understand physics or chemistry cannot understand the molecular biology of intercellular signaling or how intermolecular tethering of RNA to DNA enables ecological adaptations. Thus, like Lenski's reports, the reports of others are interpreted in the light of evolution instead of in the light of what is known about ecological variation and ecological adaptation.

It is not likely that anyone who believed in the pseudoscientific misrepresentations of mutations, natural selection, and evolution will ever learn enough about biologically-based cause and effect to be capable of intelligent discussion. Stumpy exemplifies that fact.

Lenski's reports, the reports of others are interpreted in the light of evolution instead of in the light of what is known about ecological variation and ecological adaptation

@jkand this is a blatant lie, and you know it.Lenski's study is interpreted in the light of ALL the empirical data that came before it as well as the indications that it provides proving mutations can be selected for by single populations. If this were YOUR MODEL per your descriptions to date, then ALL POPULATIONS would EQUALLY select for the adaptation and modification, and given that it is NOT true, and PROVEN thus, this means that you are selectively interpreting based upon ignorance and your personal belief system, which is, by definition, PSEUDOSCIENCE, as it attempts to alter the observations to fit the belief, instead of altering the belief to fit the data.

will ever learn enough about biologically-based cause and effect to be capable of intelligent discussion

@jk the jokethis is a perfect example of what is known as "tunnel vision" and is the reason that you cannot fathom the complexities of biological studies. You are so focused on ONE small salient point that you ASSume that it is equally applied over everything and that it means tat there are no other possible answers. TUNNEL VISIONyou ASSume that your model transcends evolution, but cannot comprehend that it is a part of the theory. TUNNEL VISIONas Anon states above

Your continued misrepresentation of Nei's statements about biophysical constraints are astounding

TUNNEL VISIONwell, that last is also considered STUPIDITY as you have been taught otherwise

therefore, the proof is in your posts! not mine. I only point out the obvious, which you IGNORE due to... that's right! TUNNEL VISION

http://www.scienc...abstract "Their coexistence involves niche construction through cross-feeding; the L ecotype grows faster on glucose but secretes by-products that S can better exploit, generating negative frequency-dependent selection. Global transcription profiling identified functional changes specific to the S lineage that appear to be important for its emergence and maintenance (14), but the mutations that caused those differences were not identified, nor were any specific differences shown to play a causal role."

Continuing to attribute to mutations what are obviously nutrient-dependent pheromone-controlled ecological adaptations in Lenski's E. coli and all other organisms is typical only of those trained by ignorant biology teachers to be their idiot minions. Anyone who is not an idiot minion or anonymous fool no longer attempts to use theory to explain biologically based cause and effect.

http://www.amazon...99661731 -- p. 196(1) Mutation is the source of all genetic variation on which any form of evolution is dependent. Mutation is the change of genomic structure and includes nucleotide substitution, insertion/deletion, segmental gene duplication, genomic duplication, changes in gene regulatory systems, transposition of genes, horizontal gene transfer, etc. (2) Natural selection is for saving advantageous mutations and eliminating harmful mutations. Selective advantage of the mutation is determined by the type of DNA change, and therefore natural selection is an evolutionary process initiated by mutation."

Lenski may have been one of the last to acknowledge the role of nutrient-dependent ecological niche construction and pheromone-controlled social niche construction. Who else, besides Nei, continues to ignore natural selection for nutrients and nutrient-dependent changes in RNA that clearly refute the pseudoscientific nonsense of evolutionary theory?

Even your designated "champions" of your anti-mutation movement, Shapiro and Noble, don't deny the contribution of mutation and Darwinian natural selection. They may downplay the relative contribution, but they don't deny it outright. Your insistence that "serious scientists" have abandoned the concept is laughable and flat out wrong.

Who else, besides Nei, continues to ignore natural selection for nutrients and nutrient-dependent changes in RNA that clearly refute the pseudoscientific nonsense of evolutionary theory?

Just about every evolutionary biologist, geneticist, biochemist, etc.

Here's an idea, James: Send out a questionnaire to a bunch of scientists, researchers, professors, etc. and see if anyone actually does reject mutation and natural selection like you claim instead of making the assumption and an ass out of yourself like you've done with everyone I've contacted.

http://www.nature...880.html and at least three other studies have characterized the full complement of RNA folding in cells with effects of secondary structures in RNA on cell type differentiation.

Those who ignore this experimental evidence of biologically based cause and effect, which was predicted in the context of our 1996 Hormones and Behavior review article (section on molecular epigenetics and alternative splicings of pre-mRNA) will need to update their knowledge-base or be considered an anonymous fool, like you are.

It makes no difference that Shapiro and Noble have not yet published anything that includes what is currently known about how the epigenetic landscape is linked directly to the physical landscape of DNA by alternative splicings of pre-mRNA. As long as they are not touting mutations, natural selection, and evolution they have nothing to prove. And those who tout pseudoscientific nonsense have proved none of it.

continues to ignore natural selection for nutrients and nutrient-dependent changes in RNA that clearly refute the pseudoscientific nonsense of evolutionary theory exemplifies the current state of ignorance exhibited by evolutionary theorists.

Others need only look at the extant literature on the birds and the bees to find experimental evidence of biologically based cause and effect that eliminates the pseudoscientific nonsense.

The links from dietary methyl donors, one-carbon metabolism and DNA methylation are perfectly clear in the context of the pheromone-controlled physiology of reproduction in species from microbes to man.

Those who ignore this experimental evidence ... will need to update their knowledge-base

Nobody is claiming that neurons are genetically different than hepatocytes. Of course epigenetics is responsible for telling your liver cells that they're liver cells and brain cells that they're brain cells, but intraorganismal cell type differentiation is not analogous to genetic changes over evolutionary time scales, mainly because one involves a static genome and the other doesn't.

As long as they are not touting mutations, natural selection, and evolution they have nothing to prove

It's so easy to tell when you don't read my links, or even more importantly, Shapiro's work.

From my link:

The role of selection is to eliminate evolutionary novelties that prove to be non-functional and interfere with adaptive needs. (p.144)

Shapiro, and every other serious scientist knows that natural selection for food enables the increasing organismal complexity manifested in morphological and behavioral phenotypes.

You can pretend that he is touting natural selection for something other than food, but no experimental evidence suggests that. The lack of experimental evidence suggests only that you are an anonymous fool who cannot process what is known about physics, chemistry, and the conserved molecular mechanisms of biologically based cause and effect in species from microbes to man.

Free copy of Shapiro's book:sunsetridgemsbiology.wikispaces.com/file/view/Evolution.A.View.from.the.21st.Century.pdf -- see the chapter that starts on page 21 for information about nutrient-dependent pheromone-controlled cell type differentiation in yeasts (i.e., microbes), which is the model I extended to humans in http://www.ncbi.n...24693353 .

'...the biological study of the brain, has succeeded in establishing a common conceptual framework that extends from cell and molecular biology, on the one hand, to brain system biology and psychology, on the other. Within this new, interdisciplinary structure, the scope of memory research ranges from genes to cognition, from molecules to mind."http://www.cell.c...)00290-6

You didn't read Shapiro's book, did you? Admit it. Nowhere in it does he deny natural selection.

The third sentence of the entire book summarizes what he's talking about:

Without variation and novelty, selection has nothing to act upon.

All he's arguing for is an expanded list of variation-producing mechanisms. He's not denying the contribution of mutation or natural selection. Directed mutagenesis, as with the SOS response, is still mutagenesis. It's not deterministic. Mutagenic polymerases are merely more error-prone, so they result in increased genetic variation. They don't make *specific* genetic changes.

He's merely advocating for the recognition of other variation-producing mechanisms alongside mutation. While the activation of these other mechanisms is not necessarily random, the resulting genetic changes still are.

He himself even says the natural genetic engineering mechanisms aren't all deterministic.

Because processing of broken ends occurs, and because NHEJmay not always join broken ends from the same site, NHEJ is aninherently mutagenic process

page 46

They produce additional variation like mutation does.

Another excerpt:

Today we think in molecular and cellular terms aboutchange processes at all levels:•Localized point mutations result from untemplated incorporations by mutagenic DNA polymerases.•Organisms acquire new biochemical routines through horizontal DNA transfers.•Major genome rearrangements result from repair of DS breaks or from the action of mobile genetic elements.•Whole genome mergers are the products of phagocytosis or cell invasions leading to endosymbiosis.

For a few antibiotics, such as streptomycin, a single mutation could modify the ribosomal target and produce resistance to a high level [690]. However, for most other antibiotics, singlemutations led to small increments of resistance so that multiple successive mutations were needed to achieve clinically significant resistance, in accord with traditional views [397][691].

The fundamental questions of where and how memory and learning are stored are answered from my model.

The most wonderful photo from the link you posted is recorded damage and repair. Every cell on earth does this. Every flash of light is testimony to damage and repair. To the memory and learning. Without some form of repair no cellular life is possible. Diversity arises when repair is no longer a match for the damage done.

With this in mind you can see where the life sciences at every step and stage of all their research is either spot on or running astray. You don't have computational models where error correction code has priority over all other code or algorithms.

Kandel never answered the two fundamental questions. All of his research is devoted to the aftermath and implementations once storage is in place. Which is Nobel Prize worthy.

There is no reason to deny the null hypothesis; no experimental evidence supports it. Regurgitating the pseudoscientific nonsense of theory is all you have ever done. If you're not going to address the experimental evidence, your comments will continue to be as worthless as those of other anonymous fools and idiot minions.

"We observe that evolutionary landscapes of RNA-protein interactionsare highly constrained, further supporting a major role for intramolecular epistasis in shaping evolutionary trajectories and providing insight into complexities of both natural and human-directed evolutionary methods for generating high-affinity ligands." http://dx.doi.org...nbt.2880

The observed biophysical constraints on RNA-protein interactions link ecological variation to ecological adaptations in species from microbes to man. There's a model for that; my model:http://www.ncbi.n...24693353

Dozens of pages of Shapiro's work where he talks about mutation and NS. The evidence is in his papers. Conveniently, they have citations of their own which you can use to track down all the experimental evidence you want!

If you're really feeling motivated, why don't you contact him yourself and ask what he thinks about your opinion that there's no evidence?

The anonymous fool always equates the mere mention of the word 'mutation' with mutation-initiated natural selection of something that results in evolution of biodiversity. Thus, everything he reads seems to somehow support the null hypothesis, which remains unsupported by experimental evidence of biologically based cause and effect.

Shapiro need only clarify that he has since learned about how "...quantitative analysis of RNA on a massively parallel array (RNA-MaP) provides generalizable insight into the biophysical basis and evolutionary consequences of sequence-function relationships." http://dx.doi.org...nbt.2880

However, even if Shapiro never clarifies what actually occurs in accord with the biophysical constraints on nutrient-dependent ecological adaptations, the constraints can no longer be ignored by anyone who is not an anonymous fool or idiot minion of some biology teacher who taught them to believe in pseudoscientific nonsense.

"...gradual mutation followed by selection has not, as a matter of fact, been demonstrated to be necessarily a cause of speciation." -- Denis Noble

If mutation-initiated natural selection had been demonstrated to be anything more than pseudoscientific nonsense invented by evolutionary theorists, the president of the International Union of Physiological Sciences would not continue to try to beat back the overwhelming number of anonymous fools and idiot minions by providing experimental evidence-based commentaries. http://www.huffin...211.html

If mutation-initiated natural selection had been demonstrated to be anything more than pseudoscientific nonsense invented by evolutionary theorists, the president of the International Union of Physiological Sciences..

You might want to start reading articles before you post them as evidence for your side:

By "replacement" I don't mean to say that the mechanism of random change followed by selection does not exist as a possible mechanism. But it becomes one mechanism amongst many others, and those mechanisms must interact.

My grateful Thanks to anonymous_9001.Never once did he go astray with a single reply to you.A person of high caliber, integrity, honesty, and patience.To which anyone can consider themselves lucky to have an exchanged of words.With one exception - you consider yourself not lucky. Too bad.

...it becomes one mechanism amongst many others, and those mechanisms must interact.

Random change followed by selection cannot occur in the absence of nutrient-dependent pheromone-controlled reproduction, which makes mutation-initiated natural selection a ridiculous proposal in the context of everything currently known about the biophysical constraints on biodiversity.

Only idiots remain to comment on experimental evidence presented here. I give up!